Exercise-induced immunosuppression: roles of reactive oxygen species and 5-AMP-activated protein kinase dephosphorylation within immune cells
Author
Hughes, Michael G.
Potter, Stephen
Sims, Craig
Butcher, Lee
Davies, Nia
Verheggen, Kenneth
Jones, Ken
Thomas, Andrew
Webb, Richard
Date
2010Type
Article
Publisher
American Physiological Society
ISSN
8750-7587
Metadata
Show full item recordAbstract
We previously proposed 5′-AMP-activated protein kinase (AMPK) dephosphorylation within immune cells as an intracellular mechanism linking exercise and immunosuppression. In this study, AMPK phosphorylation underwent transient (<1 h) decreases (53.8 ± 7.2% basal) immediately after exercise (45 min of cycling at 70% VO2max) in a cohort of 16 adult male participants. Similar effects were seen with running. However, because exercise-induced inactivation of AMPK was previously shown to occur in an AMP-independent manner, the means by which AMPK is inactivated in this context is not yet clear. To investigate the hypothesis that exercise-induced inactivation of AMPK is mediated via signaling mechanisms distinct from changes in cellular AMP-to-ATP ratios, reactive oxygen species (ROS) and intracellular Ca2+ signaling were investigated in mononuclear cells before and after exercise and in cultured monocytic MM6 cells. In in vitro studies, treatment with an antioxidant (ascorbic acid, 4 h, 50 μM) decreased MM6 cell intracellular ROS levels (88.0 ± 5.2% basal) and induced dephosphorylation of AMPK (44.7 ± 17.6% basal). By analogy, the fact that exercise decreased mononuclear cell ROS content (32.8 ± 16.6% basal), possibly due to downregulation (43.4 ± 8.0% basal) of mRNA for NOX2, the catalytic subunit of the cytoplasmic ROS-generating enzyme NADPH oxidase, may provide an explanation for the AMPK-dephosphorylating effect of exercise. In contrast, exercise-induced Ca2+ signaling events did not seem to be coupled to changes in AMPK activity. Thus we propose that the exercise-induced decreases in both intracellular ROS and AMPK phosphorylation seen in this study constitute evidence supporting a role for ROS in controlling AMPK, and hence immune function, in the context of exercise-induced immunosuppression.
Journal/conference proceeding
Journal of Applied Physiology
Citation
Moir, H., Hughes, M.G., Potter, S., Sims, C., Butcher, L.R., Davies, N.A., Verheggen, K., Jones, K.P., Thomas, A.W. and Webb, R. (2010) 'Exercise-induced immunosuppression: roles of reactive oxygen species and 5′-AMP-activated protein kinase dephosphorylation within immune cells', Journal of Applied Physiology, 108(5), pp.1284-1292.
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